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H Oosterhuis

Publications and source records attributed to H Oosterhuis.

14 recordsLinked to original sources

Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes.

BACKGROUND: Slow-channel congenital myasthenic syndromes (SCCMS) typically show dominant inheritance. They are caused by missense mutations within the subunits of muscle nicotinic acetylcholine receptors (AChR) that result in prolonged ion channel activations. SCCMS mutations within the AChR subunit are located in various functional domains, whereas fully described mutations in AChR non- subunits have, thus far, been located only in the M2 channel-lining domain. The authors identified and characterized two -subunit mutations, located outside M2, that underlie SCCMS in three kinships. In two of the three kinships, the syndrome showed an atypical inheritance pattern. METHODS: These methods included clinical diagnosis, mutation detection, haplotype analysis, and functional expression studies using single-channel recordings of mutant AChR transiently transfected into HEK293 cells. RESULTS: The authors identified two SCCMS mutations in the AChR subunit, L78P and L221F. Both mutations prolonged ACh-induced ion channel activations. L78P is present in a consanguineous family and appears to be pathogenic only when present on both alleles, and L221F shows variable penetrance in one of the two families that were identified harboring this mutation. CONCLUSION: SCCMS mutations may show a recessive inheritance pattern and variable penetrance. A diagnosis of SCCMS should not be ruled out in cases of CMS with an apparent recessive inheritance pattern.

Adolescent↗

Mutations in different functional domains of the human muscle acetylcholine receptor alpha subunit in patients with the slow-channel congenital myasthenic syndrome.

Congenital myasthenic syndromes are a group of rare genetic disorders that compromise neuromuscular transmission. A subset of these disorders, the slow-channel congenital myasthenic syndrome (SCCMS), is dominantly inherited and has been shown to involve mutations within the muscle acetylcholine receptor (AChR). We have identified three new SCCMS mutations and a further familial case of the alpha G153S mutation. Single channel recordings from wild-type and mutant human AChR expressed in Xenopus oocytes demonstrate that each mutation prolongs channel activation episodes. The novel mutations alpha V156M, alpha T254I and alpha S269I are in different functional domains of the AChR alpha subunit. Whereas alpha T254I is in the pore-lining region, like five of six previously reported SCCMS mutations, alpha S269I and alpha V156M are in extracellular domains. alpha S269I lies within the short extracellular sequence between M2 and M3, and identifies a new region of muscle AChR involved in ACh binding/channel gating. alpha V156M, although located close to alpha G153S which has been shown to increase ACh binding affinity, appears to alter channel function through a different molecular mechanism. Our results demonstrate heterogeneity in the SCCMS, indicate new regions of the AChR involved in ACh binding/channel gating and highlight the potential role of mutations outside the pore-lining regions in altering channel function in other ion channel disorders.

Adolescent↗

Christian social policy and homosexuality in The Netherlands, 1900-1970.

This essay explores the historical process in which homosexuality became an object for pastoral, medical, and mental health care in the Dutch Catholic community during the twentieth century. The confrontation between a moral-religious approach and the professional (medical and psychological) treatment of homosexuality is the central issue. In a continuing dialogue and a process of changing power relations between clergymen, physicians, psychiatrist, psychologists, and pedagogues as well as Catholic homosexuals themselves, homosexuality was transformed from sin and pathology into a psychological and social problem that could be treated in pastoral and mental health care. The changing attitudes of Catholics towards homosexuality can be explained in the context of the changing relations between religion on the one hand and health care on the other hand. Current viewpoints resulting from sociohistorical studies on the development of the medical and welfare professions have concluded that religion lost importance in modern society because physicians, psychiatrists, psycho-therapists, and social workers not only created new areas of intervention in people's private lives, but also took over the traditional tasks of the church in the field of charity and pastoral care. Medical anamnesis, psychoanalysis, and psychotherapy took the place of confession and pastoral care, thus the argument runs, and remission of sins and redemption were replaced by health and welfare. However, especially in the case of the development of the Dutch welfare state, there was a more complicated interplay between changing religious values and professional strategies. In the Netherlands professional health care and welfare institutions often were organized in a religious context and it is difficult to make a clear differentiation between religious and moral discourses on the one hand and medical and psychological ones on the other hand. Moreover, professional interventions did not take the place of pastoral care; it appears that pastoral care for homosexuals gained ground and was intensified after medical and psychological definitions of homosexuality had found acceptance in the Catholic community. Professional strategies did not supersede religion, but rather contributed to a moral re-orientation and a new pattern of Christian values and appreciations in the field of sexuality.

Attitude↗

Leftist sexual politics and homosexuality: a historical overview.

For almost a full century now, the revolutionary prospect of socialism has fuelled opening forays first of the homosexual emancipation and later of the gay liberation movements, both in Europe and in North America. It inspired Edward Carpenter and Magnus Hirschfeld at the turn of the century; André Gide and Richard Linsert in the post-World War I years; Harry Hay and Jim Kepner in the post-World War II era; and the British and American Gay Liberation Front, the Italian Fuori!, the French FHAR, the German "Rotzschwule," and the Dutch Red Faggots following the Stonewall rebellion. While the official socialist parties of Northwestern Europe may have made only limited contributions to homosexual emancipation, they certainly have a better record than conservative and Christian parties and even the liberals, who have consistently, if contradictorily, underlined the freedom of private life. Even so, parties across the entire political spectrum have gradually come to endorse at least some of the movement's goals. As it has advanced, the gay movement has changed as well, and it now finds itself pulled in divergent directions. Gay leftists who still subscribe to the ideals expressed in Marxist and utopian socialist writings now find themselves at demonstrations shoulder-to-shoulder with members of ACT UP and Queer Nation, to say nothing of gay conservatives and gay Christians. The successes achieved by the contemporary gay movement despite or precisely because of its diversity support Foucault's argument that "there is no single locus of great Refusal, no soul of revolt, source of all rebellions, or pure law of the revolutionary. Instead there is a plurality of resistances, each of them a special case...." At the close of the twentieth century, the welfare state has reached its apogee in Northwestern Europe. As blue-collar workers historically committed to class struggle have become relatively well-to-do and minoritarian, socialist parties have increasingly lost their traditional base of support and been forced into the defensive. Depending only on the socialists would mean relying on an ineffectual partner, for nowhere are they in a stable position of power. Long before the collapse of "really existing socialism" in Eastern Europe and the former Soviet Union, gay and lesbian movements began developing their own autonomous politics independent of parties. They moved in this direction in part because the coalition with leftism so frequently led to disappointment, particularly when gays and lesbians working within socialist parties were called upon to subordinate or abandon their own goals in favor of party platforms. In other cases the gay-left coalition failed to yield results because a single-minded reliance on one party placed limits on lobbying other parties and entering compromises. We have reached a time when inherited ideologies are no longer capable of laying claim to the undivided loyalty of the gay movement, if indeed they ever were. As it has developed autonomous theories and practices, the gay movement's choice of coalition partners has increasingly come to be based on pragmatism and success in advancing the gay agenda. Indeed, the roles of the gay movement and political parties have undergone a notable switch in recent years, with parties currying the support of the gay movement rather than vice versa. This signals a shift from the desire for politics to a politics of desire, going far beyond traditional socialist ideologies.

Europe↗

The "Jews" of the antifascist left: homosexuality and socialist resistance to Nazism.

In the early 1930s, German Social Democrats and Communists seized upon the homosexual orientation of some Nazi leaders, especially Ernst Röhm, with the aim of discrediting the entire National Socialist movement. In Western Europe as well as the Soviet Union, there was a general tendency among socialists in the 1930s to identify homosexuality with Nazism. Antifascist leftists created the impression that homosexuality was widespread in Nazi organizations. Such socialist theorists as Wilhelm Reich tended to view homosexuality sociologically and psychologically as a typical rightist, nationalist, and above all fascist aberration. Leftist aversion to homosexuality was not only an expression of political opportunism. Prejudices against homosexuality were part and parcel of socialist thinking and became even more deep-rooted among leftists as a consequence of the ideological and moral confrontation with National Socialism. Against the presumed immortality and perversion of the Nazis, the antifascists stressed their own rationality and purity.

Germany↗

Spontaneous platelet aggregation in cerebrovascular disease.

50 patients from a group of 130 patients with transient ischaemic attacks or cerebral infarction were found to demonstrate in vitro spontaneous platelet aggregation (SPA) while 80 normal subjects tested never showed this phenomenon. The following additional findings point towards a possible platelet abnormality: 1. Platelets from 10 patients with SPA when isolated and resuspended in normal plasma still demonstrated SPA while isolated normal platelets resuspended in patient's plasma did not. 2. Platelets demonstrating SPA showed an increased aggregation tendency upon incubation with ADP while normal platelets developed the expected refractory state. SPA was found to be dependant upon the presence of divalent cations and could further be inhibited by phentolamine and adenosine. Aspirin effectively abolished SPA in 50 patients and relieved the clinical symptoms of patients with recurrent complaints of transient blindness and paraesthesia.

Adenosine↗

Neurogenic muscle involvement in myasthenia gravis. A clinical and histopathological study.

An investigation was made into the occurrence of muscular atrophy and muscular pathology in a series of 170 patients with myasthenia gravis. The results can be summarized as follows: (1) Of the 148 patients with generalized myasthenia gravis, 14 showed local muscular atrophies. Of 10 biopsies from atrophic muscles, eight showed neurogenic changes, with or without lymphocytic infiltrations. One biopsy showed lymphocytic infiltrations only, and one showed type II-fibre atrophy (Table 1). No relationship was demonstrable between the presence of clilnical muscular atrophy and age, sex, duration of the disease, severity of the disease, presence of a thymoma, or drug resistant ophthalmoplegia. (2) In this group of patients 61 biopsies were examined from 46 individuals; 40 of these biopsies were taken from the quadriceps muscle. A thymoma was present in 17 patients. Examination disclosed neurogenic changes in 17 biopsies, lymphocytic infiltrates in 21, and myositis in one biopsy (Table 2). A distinct correlation was established between the presence of a thymoma and lymphocytic infiltrates, but none was demonstrable between thymoma and neurogenic changes (Table 3). (3) An enzyme-histochemical study was carried out in 35 cases, including 12 with neurogenic changes. A normal differentiation of type I- and type II-fibres was observed in eight instances, type grouping of type II-fibres in three, and type II-fibre atrophy in two cases. (4) In 21 patients and 19 controls, the smallest mean diameter was determined in the quadriceps muscle. Both type I- and type II-fibres proved to have a smaller mean diameter in the female patients than in the controls. In the male patients this could not be proven. (5) Of the eight patients who had died without disorders of ventilation, 90 muscle specimens were examined postmortem. Four of these patients had a thymoma. Lymphocytic infiltrations, found in 32 biopsy specimens, were mostly observed in the presence of a thymoma. Neurogenic changes were apparently unrelated to the presence of a thymoma (Tables 5 and 6). The post mortem examination included the spinal cord in five, and peripheral nerves in three cases. No abnormalities were found. (6) The muscular atrophy found in patients with myasthenia is not a myopathy but an affection of the lower motor neurone. Neurogenic changes were regularly found in the muscles of patients with myasthenia, even without muscular atrophy. The finding of these changes is no reason to reject the diagnosis. It is postulated that denervation occurs at the neuromuscular junction as a result of permanent absence of acetylcholine.

Adolescent↗